Lifetime ovulatory years and risk of epithelial ovarian cancer: a multinational pooled analysis.
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Fu Zhuxuan, Brooks Maria Mori, Irvin Sarah, Jordan Susan, Aben Katja K H, Anton-Culver Hoda, Bandera Elisa V, Beckmann Matthias W, Berchuck Andrew, Brooks-Wilson Angela, Chang-Claude Jenny, Cook Linda S, Cramer Daniel W, Cushing-Haugen Kara L, Doherty Jennifer A, Ekici Arif B, Fasching Peter A, Fortner Renée T, Gayther Simon A, Gentry-Maharaj Aleksandra, Giles Graham G, Goode Ellen L, Goodman Marc T, Harris Holly R, Hein Alexander, Kaaks Rudolf, Kiemeney Lambertus A, Köbel Martin, Kotsopoulos Joanne, Le Nhu D, Lee Alice W, Matsuo Keitaro, McGuire Valerie, McLaughlin John R, Menon Usha, Milne Roger L, Moysich Kirsten B, Pearce Celeste Leigh, Pike Malcolm C, Qin Bo, Ramus Susan J, Riggan Marjorie J, Rothstein Joseph H, Schildkraut Joellen M, Sieh Weiva, Sutphen Rebecca, Terry Kathryn L, Thompson Pamela J, Titus Linda, van Altena Anne M, White Emily, Whittemore Alice S, Wu Anna H, Zheng Wei, Ziogas Argyrios, Taylor Sarah E, Tang Lu, Songer Thomas, Wentzensen Nicolas, Webb Penelope M, AOCS Group, Risch Harvey A, Modugno Francesmary
Аннотация
METHODS: LOY was calculated using 12 algorithms. Odds ratios (ORs) and 95% confidence intervals (CIs) estimated the association between LOY or LOY components and EOC among 26 204 control participants and 21 267 case patients from 25 studies. To assess whether LOY components act through ovulation suppression alone, we compared beta coefficients obtained from regression models with expected estimates assuming 1 year of ovulation suppression has the same effect regardless of source.
RESULTS: LOY was associated with increased EOC risk (OR per year increase = 1.014, 95% CI = 1.009 to 1.020 to OR per year increase = 1.044, 95% CI = 1.041 to 1.048). Individual LOY components, except age at menarche, also associated with EOC. The estimated model coefficient for oral contraceptive use and pregnancies were 4.45 times and 12- to 15-fold greater than expected, respectively. LOY was associated with high-grade serous, low-grade serous, endometrioid, and clear cell histotypes (ORs per year increase = 1.054, 1.040, 1.065, and 1.098, respectively) but not mucinous tumors. Estimated coefficients of LOY components were close to expected estimates for high-grade serous but larger than expected for low-grade serous, endometrioid, and clear cell histotypes.
CONCLUSIONS: LOY is positively associated with nonmucinous EOC. Differences between estimated and expected model coefficients for LOY components suggest factors beyond ovulation underlie the associations between LOY components and EOC in general and for non-HGSOC.